Cathepsin K (CatK) is a cysteine protease known for its potent collagenolytic activity, being recognized as an important target to the development of therapies for the treatment of bone disorders. Epoxypeptidomimetics have been reported as potent inhibitors of cathepsins, thus in this work we present a green synthesis of new peptidomimetics by using a one-pot asymmetric epoxidation/Ugi multicomponent reaction. The compounds were evaluated against CatK showing selectivity when compared with cathepsin L, with an inhibition profile in the low micromolar IC₅₀ range. Investigation of the mechanism of action carried out for compounds LSPN428 and LSPN694 suggested a mixed inhibition mode and docking studies allowed a better understanding about interactions of inhibitors with the enzyme.

组织蛋白酶K（CatK）是一种半胱氨酸蛋白酶，以其强大的胶原蛋白分解活性而闻名，被认为是开发治疗骨病的重要药物。已报道环氧肽模拟物是组织蛋白酶的有效抑制剂，因此在这项工作中，我们通过使用一锅式不对称环氧化/ Ugi多组分反应，绿色合成了新的肽模拟物。与组织蛋白酶L相比，针对CatK表现出选择性的化合物进行了评估，其抑制谱在低微摩尔IC ₅₀范围内。研究化合物LSPN428和LSPN694的作用机理 建议混合抑制模式和对接研究可以更好地了解抑制剂与酶的相互作用。